Species-specificity of the secondary biosynthetic potential in Bacillus

Qun-Jian Yin; Ti-Ti Ying; Zhen-Yi Zhou; Gang-Ao Hu; Cai-Ling Yang; Yi Hua; Hong Wang; Bin Wei

doi:10.3389/fmicb.2023.1271418

Species-specificity of the secondary biosynthetic potential in Bacillus

Front Microbiol. 2023 Oct 23:14:1271418. doi: 10.3389/fmicb.2023.1271418. eCollection 2023.

Authors

Qun-Jian Yin^#¹, Ti-Ti Ying^#², Zhen-Yi Zhou², Gang-Ao Hu², Cai-Ling Yang², Yi Hua², Hong Wang², Bin Wei²

Affiliations

¹ Fourth Institute of Oceanography, Ministry of Natural Resources, Beihai, China.
² College of Pharmaceutical Science and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Key Laboratory of Marine Fishery Resources Exploitation and Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou, China.

^# Contributed equally.

Abstract

Introduction: Although Bacillus species have produced a wide variety of structurally diverse and biologically active natural products, the secondary biosynthetic potential of Bacillus species is widely underestimated due to the limited number of biosynthetic gene clusters (BGCs) in this genus. The significant variation in the diversity and novelty of BGCs across different species within the Bacillus genus presents a major obstacle to the efficient discovery of novel natural products from Bacillus.

Methods: In this study, the number of each class of BGCs in all 6,378 high-quality Bacillus genomes was predicted using antiSMASH, the species-specificity of BGC distribution in Bacillus was investigated by Principal component analysis. Then the structural diversity and novelty of the predicted secondary metabolites in Bacillus species with specific BGC distributions were analyzed using molecular networking.

Results: Our results revealed a certain degree of species-specificity in the distribution of BGCs in Bacillus, which was mainly contributed by siderophore, type III polyketide synthase (T3PKS), and transAT-PKS BGCs. B. wiedmannii, B. thuringiensis, and B. cereus are rich in RiPP-like and siderophore BGCs, but lack T3PKS BGCs, while B. amyloliquefaciens and B. velezensis are abundant in transAT-PKS BGCs. These Bacillus species collectively encode 77,541 BGCs, with NRPS and RiPPs being the two most dominant types, which are further categorized into 4,291 GCFs. Remarkably, approximately 54.5% of GCFs and 93.8% of the predicted metabolite scaffolds are found exclusively in a single Bacillus species. Notably, B. cereus, B. thuringiensis, and B. velezensis exhibit the highest potential for producing species-specific NRPS and PKS bioinformatic natural products. Taking two species-specific NRPS gene clusters as examples, the potential of Bacillus to synthesize novel species-specific natural products is illustrated.

Conclusion: This study highlights the species-specificity of the secondary biosynthetic potential in Bacillus and provides valuable insights for the targeted discovery of novel natural products from this genus.

Keywords: Bacillus; biosynthetic potential; genome mining; natural products; species-specificity.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by the Public Welfare Technology Application Research project of Zhejiang Provincial Science (LGD21C040005), the programs of the National Natural Science Foundation of China (Nos. 42276137 and 42106127), the Fundamental Research Funds for the Provincial Universities of Zhejiang (No. RF-A2022013), and the Guangxi Natural Science Foundation (No. 2020GXNSFBA297008).